PMID- 14559718
OWN - NLM
STAT- MEDLINE
DCOM- 20040224
LR  - 20191210
IS  - 1931-857X (Print)
IS  - 1522-1466 (Linking)
VI  - 286
IP  - 2
DP  - 2004 Feb
TI  - Extracellular matrix regulates glomerular epithelial cell survival and 
      proliferation.
PG  - F255-66
AB  - Glomerular epithelial cell (GEC) injury and apoptosis may contribute to sclerosis 
      in glomerulonephritis. The present study addresses signals that regulate survival 
      of GEC in culture and in the acute puromycin aminonucleoside nephrosis (PAN) 
      model of GEC injury in vivo. Compared with GEC on plastic substratum, adhesion to 
      collagen increased activation of focal adhesion kinase (FAK), c-Src, and ERK and 
      facilitated survival (prevented apoptosis). GEC on plastic exhibited increased 
      caspase-8 and -9 activities, increased expression of the proapoptotic protein, 
      Bax, and decreased the antiapoptotic protein, Bcl-XL, compared with collagen. 
      Stable expression of constitutively active mutants of FAK (CD2-FAK) or MEK 
      (R4F-MEK) activated the ERK pathway and supplanted the requirement of collagen 
      for survival. In contrast, expression of a Ras mutant that activates 
      phosphatidylinositol 3-kinase but blocks ERK activation or pharmacological 
      inhibition of the ERK pathway decreased survival on collagen. Glomeruli isolated 
      from rats with PAN revealed increased beta1-integrin expression, along with 
      increased activation of FAK, c-Src, and ERK, compared with controls. EGF receptor 
      activation was undetectable in PAN. Therefore, adhesion to collagen, resulting in 
      activation of FAK and the Ras-ERK pathway, supports GEC survival. Analogous 
      signals for GEC survival are activated in PAN.
FAU - Bijian, Krikor
AU  - Bijian K
AD  - Department of Medicine, McGill university Health Centre, Montreal, Quebec, Canada 
      H3A 1A1.
FAU - Takano, Tomoko
AU  - Takano T
FAU - Papillon, Joan
AU  - Papillon J
FAU - Khadir, Abdelkrim
AU  - Khadir A
FAU - Cybulsky, Andrey V
AU  - Cybulsky AV
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20031014
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Bax protein, rat)
RN  - 0 (Bcl2l1 protein, rat)
RN  - 0 (Growth Substances)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 0 (bcl-X Protein)
RN  - 58-60-6 (Puromycin Aminonucleoside)
RN  - 9007-34-5 (Collagen)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (CSK Tyrosine-Protein Kinase)
RN  - EC 2.7.10.2 (Focal Adhesion Kinase 1)
RN  - EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Ptk2 protein, rat)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinases)
RN  - EC 3.4.22.- (Caspases)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Animals
MH  - CSK Tyrosine-Protein Kinase
MH  - Caspases/metabolism
MH  - Cell Adhesion/drug effects/physiology
MH  - Cell Division/physiology
MH  - Cell Survival/drug effects/physiology
MH  - Cells, Cultured
MH  - Collagen/pharmacology
MH  - Enzyme Activation/drug effects
MH  - Extracellular Matrix/*metabolism
MH  - Focal Adhesion Kinase 1
MH  - Focal Adhesion Protein-Tyrosine Kinases
MH  - Gene Expression Regulation, Enzymologic
MH  - Growth Substances/pharmacology
MH  - Kidney Glomerulus/*cytology/*metabolism
MH  - MAP Kinase Kinase Kinases/genetics/metabolism
MH  - MAP Kinase Signaling System/physiology
MH  - Male
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Nephrosis/chemically induced/metabolism
MH  - Protein-Tyrosine Kinases/genetics/metabolism
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Puromycin Aminonucleoside
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - bcl-2-Associated X Protein
MH  - bcl-X Protein
MH  - ras Proteins/metabolism
MH  - src-Family Kinases
EDAT- 2003/10/16 05:00
MHDA- 2004/02/26 05:00
CRDT- 2003/10/16 05:00
PHST- 2003/10/16 05:00 [pubmed]
PHST- 2004/02/26 05:00 [medline]
PHST- 2003/10/16 05:00 [entrez]
AID - 00259.2003 [pii]
AID - 10.1152/ajprenal.00259.2003 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2004 Feb;286(2):F255-66. doi: 
      10.1152/ajprenal.00259.2003. Epub 2003 Oct 14.